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| Name | Class |
|---|---|
| Turning Point | OTHER |
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Heavy cannabis use is associated with substantive learning and memory impairments and elevated risk of psychopathology. It has been repeatedly demonstrated that the hippocampus, centrally implicated in these processes, is particularly vulnerable to the deleterious effects of prolonged exposure to cannabis. This deterioration of hippocampal structure, function, and biochemistry can be reversed, but this requires two or more years of abstinence from cannabis. However, most heavy cannabis users find it extremely difficult to maintain abstinence over extended periods and current treatments for cannabis use disorders are inadequate. There is a pressing clinical need for an intervention that rapidly accelerates hippocampal recovery, ameliorates the associated cognitive impairments and mental health symptoms, and leads to improved treatment outcomes. One promising candidate is physical exercise. In addition to the well-known physical health benefits, regular exercise also has a potent positive effect on brain health. The current study will investitive the capacity of two different neuroscientifically-informed 12-week exercise programs can restore brain health for heavy long term cannabis users.
Heavy cannabis use is associated with substantive learning and memory impairments and elevated risk of psychopathology. It has been repeatedly demonstrated that the hippocampus, centrally implicated in these processes, is particularly vulnerable to the deleterious effects of prolonged exposure to cannabis. This deterioration of hippocampal structure, function, and biochemistry can be reversed, but this requires two or more years of abstinence from cannabis. However, most heavy cannabis users find it extremely difficult to maintain abstinence over extended periods and current treatments for cannabis use disorders are inadequate. There is a pressing clinical need for an intervention that rapidly accelerates hippocampal recovery, ameliorates the associated cognitive impairments and mental health symptoms, and leads to improved treatment outcomes. One promising candidate is physical exercise. In addition to the well-known physical health benefits, regular exercise also has a potent positive effect on brain health and can increase the size of the hippocampus. It's not yet known how much or what kind of exercise produces the best results. This study has been designed to compare the effects of two different exercise programs.
The research team are investigating whether the programs have a positive impact on brain health and, if they do, whether one is more effective than the other. The research team will also measure whether engaging in either program leads to a reduction in cannabis consumption, and improvements in thinking skills, mental health, and general wellbeing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High Intensity Physical Training | Active Comparator | 12-week, 36 session, cardiorespiratory-focussed physical exercise program delivered by an accredited exercise physiologist |
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| Low Intensity Physical Training | Active Comparator | 12- week, 36 session, strength-focussed physical exercise program delivered by an accredited exercise physiologist |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High Intensity Interval Training | Behavioral | Exercise sessions will commence with an initial 3-week accustomization period whereby training load will increase incrementally from 2 x 45min sessions with effort peaking at 60% VO2 max (week 1) increasing to 3 x 45minute with effort peaking at 80% VO2max (week 3). Participants will transition to the full HIIT protocol for the remaining weeks. The HIIT component will comprise a work-rest ratio of ≥1:1minutes, with alternating exertion epochs at >80% VO2max and <60% VO2max. As VO2max is likely to increase as fitness improves toward the end of the 3-month program, adjustments to HIIT will be made by the exercise physiologist based on real-time heart rate monitoring, ensuring greater accuracy in participants achieving their heart rate targets. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in hippocampal integrity | Composite score derived from three hippocampal health indices: volume (structural MRI), connectivity (DTI), neuronal health (MRS NAA) calculated as described in Yucel et al (2016), doi:10.1038/tp.2015.201. | Baseline (0 months), post (3 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in cannabis use | Time line follow back | Baseline (0 months), post (3 months), follow up (6 months) |
| Change in cannabis dependence | Severity of Dependence Scale (SDS; range = 0-15 higher scores indicate higher dependence |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Murat Yucel | Monash University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Monash University, BrainPark | Melbourne | Victoria | 3800 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40928796 | Derived | Richardson KE, Suo C, Albertella L, Maleki S, Coxon J, Hendrikse J, Hughes S, Pitt J, Kayayan E, Brown C, Nguyen L, Solowij N, Lubman DI, Segrave R, Yucel M. High-Intensity Exercise and Hippocampal Integrity in Adults With Cannabis Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Dec 1;82(12):1240-1245. doi: 10.1001/jamapsychiatry.2025.2319. |
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| ID | Term |
|---|---|
| D008224 | Lymphoma, Follicular |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000072696 | High-Intensity Interval Training |
| D055070 | Resistance Training |
| ID | Term |
|---|---|
| D064797 | Physical Conditioning, Human |
| D015444 | Exercise |
| D009043 | Motor Activity |
| D009068 | Movement |
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| Strength and Resistance Training | Behavioral | Exercise sessions will comprise a combination of strength, coordination and mobility exercises. The strength component will consist of 2-3 sets of resistance exercises at ≤70% of a predicted 1 repetition maximum, targeting all body segments. Heart rate tracking will occur to ensure participants do not exceed 70% v02 (or exceed Lactate Threshold). |
|
| Baseline (0 months), post (3 months), follow up (6 months) |
| Change in cannabis craving | Penn Craving Scale (PCS; range = 0 - 30 higher scores indicate greater craving) | Baseline (0 months), post (3 months), follow up (6 months) |
| Change in depression symptoms | Quick Inventory of Depressive Symptomology (QUIDS; range = 0 - 27 higher scores indicate greater depression symptom severity) | Baseline (0 months), post (3 months), follow up (6 months) |
| Change in anxiety symptoms | StateTrait Anxiety Inventory (STAI; range = 20 to 80, higher scores indicate greater anxiety) | Baseline (0 months), post (3 months), follow up (6 months) |
| Change in resilience | Connor David Resilience Scale (CDRS; range = 0-100 higher scores indicate higher resilience) | Baseline (0 months), post (3 months), follow up (6 months) |
| Change in coping skills | Perceived Stress Scale (10 item; range = 0 - 40 higher scores indicate greater stress) | Baseline (0 months), post (3 months), follow up (6 months) |
| Change in sleep quality | Pittsburgh Sleep Quality Index (PSQI; range = 0 to 21 higher scores indicate worse sleep quality) | Baseline (0 months), post (3 months), follow up (6 months) |
| Change in mental wellbeing | Warwick Edinburgh Mental Wellbeing Scale (WEMWBS; range = 14-70 higher scores indicate increased mental well being) | Baseline (0 months), post (3 months), follow up (6 months) |
| Change in quality of life | Quality of Life and Satisfaction Questionnaire - Short Form (QOL-SF; range = 70 higher scores indicate greater life satisfaction and enjoyment) | Baseline (0 months), post (3 months), follow up (6 months) |
| Change in memory | Rey Auditory Verbal Learning Test (RAVLT) | Baseline (0 months), post (3 months), follow up (6 months) |
| Change in associative memory | Paired Associates Learning Task (PAL) | Baseline (0 months), post (3 months), follow up (6 months) |
| Change in visual memory | Figural Memory Tasks | Baseline (0 months), post (3 months) |
| Change in cardiorespiratory fitness | VO2 max | Baseline (0 months), post (3 months) |
| D008232 |
| Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D009142 |
| Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
| D005081 | Exercise Therapy |
| D012046 | Rehabilitation |
| D000359 | Aftercare |
| D003266 | Continuity of Patient Care |
| D005791 | Patient Care |
| D013812 | Therapeutics |
| D026741 | Physical Therapy Modalities |